Non-inferiority Study of Safety and Efficacy of Everolimus With Low Dose Tacrolimus to Mycophenolate Mofetil With Standard Dose Tacrolimus in Kidney Transplant Recipients
- Conditions
- Kidney Transplant
- Interventions
- Registration Number
- NCT01025817
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this phase 3b study is to compare the safety and efficacy of everolimus with low dose tacrolimus to mycophenolate mofetil with standard dose tacrolimus in kidney transplant recipients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 613
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mycophenolate mofetil & standard dose tacrolimus mycophenolate mofetil and tacrolimus Mycophenolate mofetil and tacrolimus (MMF) treatment arm: MMF dose was initiated at 1 g b.i.d. (2 g/day). Adjustments were to be made for adverse events including, but not limited to, gastrointestinal intolerance and decrease in WBC. MMF trough or AUC was not used to adjust dosing. In this group, tacrolimus was initiated according to local practice. Tacrolimus dose was adjusted from Day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 12 ng/mL. From Month 2 until Month 6, target tacrolimus trough level was reduced to 7 - 10 ng/mL. After Month 6, target level of tacrolimus was reduced to 5 - 8 ng/mL. Everolimus (EVR) & low dose of tacrolimus Everolimus and tacrolimus Everolimus (EVR) and tacrolimus treatment arm: Therapeutic drug monitoring of everolimus and tacrolimus was mandatory throughout the study. From Day 5 onwards, the everolimus 0.75 mg b.i.d. dose was increased if the trough level was \< 3 ng/mL, or reduced if the trough level was \> 8 ng/mL. Tacrolimus was initiated according to local practice. In this treatment arm, the tacrolimus dose was adjusted from Day 3 onwards, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From Month 2 until Month 6, the target tacrolimus trough level was 3 ng/mL to 6 ng/mL. After Month 6, the tacrolimus dose was adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL.
- Primary Outcome Measures
Name Time Method Number of Participants With Incidence of Composite Efficacy Failure 12 Months Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, (3) participant death or(4) loss to follow-up. \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis.
- Secondary Outcome Measures
Name Time Method Estimated Glomerular Filtration Rate (eGFR) 12 Months Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
Number of Participants With Incidence of CMV (Viremia, Syndrome and Disease) 12 Months Participants with incidence of CMV (viremia, syndrome and disease). CMV is cytomegalovirus.
Number of Participants With Incidence Rates of BKV Viremia, BKV Viruria, or BKV Nephropathy 12 Months Participants with Incidence of BKV (viremia, viruria, or nephropathy). BKV is Polyomavirus type BK.
Number of Participants With Incidence of New Onset of Diabetes Mellitus 12 Months Incidence of new onset diabetes mellitus defined as non-diabetic patients before transplantation, who are receiving glucose lowering treatment for more than 30 days post-transplant, or with a random plasma glucose ≥200 mg dL (11.1 mmol/L) with 2 fasting plasma glucose values ≥126 mg/dL (7 mmol/L)
Number of Participants With Incidence of Proteinuria Events Baseline and 12 Months Number of participants with Incidence of proteinuria events indicating chronic kidney disease
Number of Participants With Incidence of Adverse Events, Serious Adverse Events, and Tacrolimus-associated Adverse Events 12 Months Incidence of adverse events, serious adverse events, and tacrolimus-associated adverse events by System Organ Class
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇦Montreal, Quebec, Canada